Scientists have β new insulin signal suppressors in cells

is a well-known endocrine disease, and the prevalence and incidence of diabetes have risen sharply globally, threatening human health. However, the specific cause and pathogenesis are not clear, may be the combination of genetic and environmental factors, due to the immune-mediated islet B cells of the selectivity of destruction. Therefore, insulin-sensitive β the pancreas and cells can protect diabetics from β cell failure.On January 27, 2021, the Heiko Lickert team at the Munich Center in Helmholtz, Germany, published an online article in the journal Nature entitled "Inceptors insulin signalling in β-cells to control glycaemia", which revealed the finding of a new insulin signaling path factor in β cells that controls blood sugar.In this article, researchers identifying new pancreatic regulators and finding that 5330417C22Rik mRNA is expressed strong in the embryonic pancreas. Its associated gene is called the estrogen-induced gene (EIG121, also known as ELAPOR1 or KIAA1324), and in mice its genes are located on chromosome 3, with 22 exons, transrestriated by three selectively clipped variants and translated into a one-way type I transfilm protein.Compared with the cysteine-rich domain (CRD) and insulin-like growth factor 1 (IGF1) in β cells, the bioinficial analysis of KIAA1324 revealed that the cysteine residue in CRD in the growth factor domain 4 was conservative. In addition, KIAA1324's ganache 6-phosphate subject (M6PR) domain is similar to cation-dependent M6PR (CD-M6PR) and cation non-dependent M6PR (CI-M6PR). Therefore, because of the similarity between KIAA1324 and INSR, IGF1R, and IGF2R in extracellulation domain and KIAA1324 inhibition function, the researchers renamed KIAA1324 insulin inhibitor (encoded by the gene Iir).Subsequently, the authors conducted a series of experiments to confirm the quality and blood sugar control of the β cells regulated by the subject, and found that mice with a lack of the gene Iir-/-showed signs of hypersurgemia and hypoglycemia and died within hours of birth. This suggests that Iir knockout leads to β cell proliferation and increased mass during pancreatic development, and affects glucose stability after birth. Molecular and cell analysis of Iir-/- mouse embryos and postpartum pancreas showed that the activation of INSR-IGF1R in Iir-/- Pancreatic tissue increased, resulting in increased proliferation and mass of β cells. Similarly, induced β-cell-specific Iir-/- knock-out in adult mice and ionosome islets led to increased activation of INSR-IGF1R and increased proliferation of β cells, thereby increasing glucose tolerance in the body.The team also conducted a mechanism study of its effects and found that the subjects made it possible to mediat the internal swallowing of mesh proteins. In terms of structure, the subject interacts with INSR-IGF1R to promote the internal swallowing of mesh proteins and desensitate the subject. The use of monoclonal antibodies against the extracellular domain of the subject blocks this physical interaction, resulting in the memory and INSR remaining on the mass membrane, thus maintaining the inSR-IGF1R in β cells.In summary, these results show that the subject protects insulin-producing β cells from the activation of the composition pathway and identifies the subject as a potential molecular target for INSR-IGF1R sensitivity and diabetes treatment. (Biological Exploration):Ansarullah, Jain, C., Far, F.F. et al. Inceptor counteracts insulin signalling in β-cells to control glycaemia. Nature (2021)[2][3]